What is the difference between Humalog (insulin lispro) and Novolog (insulin aspart)?

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Last updated: December 4, 2025View editorial policy

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Humalog vs Novolog: Clinical Differences

Humalog (insulin lispro) and Novolog (insulin aspart) are clinically interchangeable rapid-acting insulin analogs with nearly identical pharmacokinetic and pharmacodynamic profiles, though they are not FDA-approved as interchangeable products and require a prescription change to switch between them. 1

Pharmacokinetic Profile

Both insulins have essentially the same time-action characteristics:

  • Onset of action: 0.25-0.5 hours (15-30 minutes) 1, 2
  • Peak action: 1-3 hours 1, 2
  • Duration of action: 3-5 hours 1, 2

The molecular difference is minimal—insulin aspart has proline substituted with aspartic acid at position B28, while insulin lispro has the lysine and proline residues at positions B28 and B29 reversed. 3 Despite these distinct amino acid modifications, their clinical action profiles are nearly identical. 1, 2

Clinical Use and Equivalence

The American Diabetes Association recommends both insulin lispro and insulin aspart as appropriate rapid-acting insulin analogs for prandial insulin in basal-bolus regimens and continuous subcutaneous insulin infusion (insulin pumps) for both type 1 and type 2 diabetes. 1

Both insulins:

  • Provide better postprandial glucose control than regular human insulin 2
  • Reduce nocturnal and severe hypoglycemia compared to regular insulin, particularly in type 1 diabetes 2
  • Can be administered 0-5 minutes before meals 4
  • Have similar stability profiles when used in insulin pumps 1

Practical Considerations

When converting between these products, they can be dosed unit-for-unit since their pharmacodynamics are clinically equivalent. 1, 4 However, a prescription change is required because they are not designated as interchangeable products by regulatory authorities. 1

The primary practical difference is cost, which may vary between the two products and could affect patient access and adherence. 1 When one product is unavailable (such as in shortage situations), the other serves as an appropriate substitute using the same dosing strategy. 4

Common Pitfall

Do not assume these products can be automatically substituted at the pharmacy level without a new prescription—despite their clinical equivalence, they require prescriber authorization to switch. 1

References

Guideline

Insulin Aspart and Insulin Lispro Clinical Profiles

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Insulin analogues: an example of applied medical science.

Diabetes, obesity & metabolism, 2009

Guideline

Alternative Insulin Regimens

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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